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If psychedelics heal, how do they do it?

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Psychedelic drugs like MDMA and magic mushrooms are showing remarkable promise in treating serious mental health conditions like PTSD and depression, with clinical trials demonstrating higher success rates than traditional therapy alone. However, scientists still don’t fully understand how these drugs work at the molecular and brain level, or whether the hallucinations they produce are necessary for healing. Researchers are investigating whether modified versions without hallucinations could provide the same benefits while being easier to administer, while also exploring how individual factors and treatment environment affect outcomes.

Associations Between Escitalopram and Psilocybin Therapy and Brain Resting-State Functional Connectivity in Major Depressive Disorder

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This study compared how two depression treatments—a common antidepressant called escitalopram and psilocybin therapy—affect brain connectivity and depression symptoms. Both treatments reduced feelings of lacking pleasure and impulsive behaviors in depressed patients. The research found that while both worked, they affected different parts of the brain’s reward system in distinct ways, suggesting they may work through different mechanisms.

Meditation, psychedelics, and brain connectivity: A randomized controlled resting-state fMRI study of N,N-dimethyltryptamine and harmine in a meditation retreat

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Researchers studied how meditation combined with a psychedelic compound called DMT affects the brain. They scanned 40 experienced meditators before and after a 3-day retreat, with some receiving the psychedelic and others a placebo. While meditation alone reduced connections between different brain networks, the psychedelic enhanced certain connections, suggesting the two practices may complement each other in promoting mental health.

Biological markers of treatment response to serotonergic psychedelic therapies: a systematic review

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This review examines how scientists can predict which patients will benefit most from psychedelic-assisted therapy for depression by measuring biological markers in the brain and blood. Researchers found that certain brain changes and protein levels—particularly involving the amygdala, specific brain regions, and inflammation markers—appear linked to treatment success. While the current studies are small, they suggest that measuring these biological markers could eventually help doctors personalize psychedelic treatments for depression.

Transient destabilization of whole brain dynamics induced by N,N-Dimethyltryptamine (DMT)

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This study used computer models of brain activity to understand how the psychedelic drug DMT rapidly changes how the brain works during an acute experience. Researchers found that DMT pushes brain dynamics into a special state where the brain becomes hypersensitive to small changes or stimuli. This heightened sensitivity is strongest in brain regions rich in serotonin receptors and matches the expected timing of the drug’s effects, suggesting that brief psychedelic experiences may create lasting changes in the brain through this temporary destabilization window.

Psilocybin-induced changes in neural reactivity to alcohol and emotional cues in patients with alcohol use disorder: An fMRI pilot study

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This pilot study examined how psilocybin affects the brains of people with alcohol use disorder. Using brain imaging (fMRI), researchers found that psilocybin increased activity in brain regions associated with decision-making and emotional control while decreasing activity in regions linked to cravings. These findings suggest psilocybin may help people with alcohol addiction by enhancing their ability to regulate emotions and resist urges to drink.

Network control energy reductions under DMT relate to serotonin receptors, signal diversity, and subjective experience

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Researchers studied how DMT affects the brain’s ability to switch between different activity patterns. Using simultaneous brain imaging (fMRI) and electrical recordings (EEG), they found that DMT makes these transitions easier and less energy-intensive. The effects occurred primarily in brain regions with high levels of serotonin 2a receptors and were accompanied by increased complexity of brain signals and stronger subjective drug effects.

Psilocybin, an Effective Treatment for Major Depressive Disorder in Adults – A Systematic Review

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Psilocybin, a naturally occurring compound found in certain mushroom species, shows significant promise as a treatment for depression. Clinical studies reviewed in this research found that psilocybin-assisted therapy reduced depressive symptoms in every patient studied, with improvements lasting months after treatment. Unlike traditional antidepressants, psilocybin caused only mild temporary side effects and worked faster, suggesting it could become an important alternative treatment for depression.

Safety, tolerability, and clinical and neural effects of single-dose psilocybin in obsessive–compulsive disorder: protocol for a randomized, double-blind, placebo-controlled, non-crossover trial

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This study tests whether psilocybin (the active compound in certain mushrooms) can help people with obsessive-compulsive disorder who haven’t responded to standard treatments. In a carefully controlled trial, participants receive either a single dose of psilocybin or a placebo while receiving psychological support, with their brain activity and symptoms monitored. The research aims to determine if this novel treatment is safe and whether it could work faster than existing medications for this difficult-to-treat condition.

N,N-dimethyltryptamine effects on connectome harmonics, subjective experience and comparative psychedelic experiences

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Researchers studied how DMT, a powerful psychedelic drug, changes brain activity patterns and how these changes relate to what people experience. Using advanced brain imaging and network analysis, they found that DMT shifts brain activity away from large-scale network patterns toward smaller, more diverse patterns. Importantly, these brain changes directly tracked with how intensely participants reported experiencing the drug’s effects moment-to-moment.

Research Keyword: fMRI